Biomedical subjects

G L Hall

Publications and source records attributed to G L Hall.

At least 19 recordsLinked to original sources

PubMed2006

Pre-flight testing of preterm infants with neonatal lung disease: a retrospective review.

BACKGROUND: The low oxygen environment during air travel may result in hypoxia in patients with respiratory disease. However, little information exists on the oxygen requirements of infants with respiratory disease planning to fly. A study was undertaken to identify the clinical factors predictive of an in-flight oxygen requirement from a retrospective review of hypoxia challenge tests (inhalation of 14-15% oxygen for 20 minutes) in infants referred for fitness to fly assessment. METHODS: Data from 47 infants (median corrected age 1.4 months) with a history of neonatal lung disease but not receiving supplemental oxygen at the time of hypoxia testing are reported. The neonatal and current clinical information of the infants were analysed in terms of their ability to predict the hypoxia test results. RESULTS: Thirty eight infants (81%) desaturated below 85% and warranted prescription of supplemental in-flight oxygen. Baseline oxygen saturation was >95% in all infants. Age at the time of the hypoxia test, either postmenstrual or corrected, significantly predicted the outcome of the hypoxia test (odds ratio 0.82; 95% confidence intervals 0.62 to 0.95; p = 0.005). Children passing the hypoxia test were significantly older than those requiring in-flight oxygen (median corrected age (10-90th centiles) 12.7 (3.0-43.4) v 0 (-0.9-10.9) months; p < 0.0001). CONCLUSIONS: A high proportion of ex-preterm infants not currently requiring supplemental oxygen referred for fitness-to-fly assessment and less than 12 months corrected age are at a high risk of requiring in-flight oxygen. Referral of this patient group for fitness to fly assessment including a hypoxia test may be indicated.

Aerospace Medicine↗

PubMed2006

Exhaled nitric oxide is not reduced in infants with cystic fibrosis.

Fractional exhaled nitric oxide (F(eNO)) has been reported to be reduced in cystic fibrosis (CF) patients. However, data from young children are conflicting and it is not clear whether this is a primary feature of the disease or a secondary response. The present study compared F(eNO) between CF and healthy infants using a validated single-breath technique. A total of 23 healthy infants (11 females; mean age 40.1 weeks) and 18 infants with CF (nine females; 64.9 weeks) underwent tests of lung function and F(eNO). Bronchoalveolar lavage (BAL) was collected from all CF infants 2-5 days after lung function testing. There was no significant difference in F(eNO) between the CF and healthy infants (geometric mean: 23.1 parts per billion (ppb) and 17.0 ppb, respectively). There was an inverse relationship between age and F(eNO) in the CF patients, but not in the healthy group. Within the CF group, there was no association between F(eNO) and any marker of airway inflammation measured in the BAL. Exhaled nitric oxide is not reduced in cystic fibrosis infants, but does decrease with age. The current data indicate that F(eNO) is not a good marker of airway inflammation in cystic fibrosis.

Age Factors↗

PubMed2005

Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation.

BACKGROUND: Lung disease in cystic fibrosis (CF) is established in early childhood with recurrent bacterial infections and inflammation. Using spirometry, the effect of this early lung damage cannot be measured until a child is 6 years of age when some irreversible lung damage may already have occurred. Techniques for measurement of lung function in infants and young children include raised volume rapid thoracic compression (RVRTC) and low frequency forced oscillation (LFFOT). The aim of this study was to investigate the role of inflammation and infection on a population of infants and young children with CF and to determine whether lung function in this population (measured by LFFOT) is affected by early lung disease. METHODS: Lung function was measured by LFFOT in 24 children undergoing bronchoalveolar lavage (BAL) on 27 occasions as part of an annual programme while still under general anaesthesia. Following lung function testing, three aliquots of saline were instilled into the right middle or lower lobe. The first aliquot retrieved was processed for the detection of microbes, and the remaining aliquots were pooled to assess inflammatory markers (cytology, IL-8, NE, LTB(4)). RESULTS: Inflammation (percentage and number of neutrophils) was significantly higher in children with infections (p<0.001, p = 0.04, respectively), but not in those with symptoms. Several markers of inflammation significantly correlated with LFFOT parameters (R, G, and eta). CONCLUSION: Infections and inflammation are established before symptoms are apparent. Inflammation is correlated with measures of parenchymal changes in lung function measured by LFFOT.

Airway Resistance↗

PubMed2005

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma.

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.

Acetates↗

PubMed2002

Elevated nitrite in breath condensates of children with respiratory disease.

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough. Breath condensates were obtained from 66 children (43 males:23 females, 3.1-16 yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations. Patients with CF (median: 5-95% percentiles; 2.02: 0.43-6.37 microM) or asthma (2.10: 0.63-5.45 microM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13-1.83 microM; p<0.05) or subjects with cough (0.75: 0.03-1.75 microM; p<0.05). Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3 yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.

Adolescent↗

PubMed2002

Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants.

Small airway disease in infants is characterised by abnormal lung volume and uneven ventilation distribution. An inert tracer gas washin/washout technique using a pulsed ultrasonic flow meter is presented to measure functional residual capacity (FRC) and ventilation distribution in spontaneously breathing and unsedated infants. With a pulsed ultrasound sent through the main stream of the flow meter, flow, volume and MM of the breathing gas can be calculated. Sulphur hexafluoride was used as a tracer gas. In a mechanical lung model (volume range 53-188 mL) and in 12 healthy infants (aged 38.3+/-9.2 days; mean+/-SD) accuracy and reproducibility of the technique was assessed. Indices of ventilation distribution such as alveolar-based mean dilution number (AMDN) and pulmonary clearance delay (PCD) were calculated. Mean error of volume measurement in the lung model was 0.58% (coefficient of variance (CV) 1.3%). FRC was in the low predicted range for normal infants (18.0+/-2.0 mL x kg(-1)) and highly reproducible (5.5+/-1.7% intra-subject CV). AMDN was 1.63+/-0.15 and PCD was 52.9+/-11.1%. Measurement of functional residual capacity and ventilation distribution using a sulphur hexafluoride washin/washout and an ultrasonic flow meter proved to be highly accurate and reproducible in a lung model and in healthy, spontaneously breathing and unsedated infants.

Female↗

PubMed2001

Altered respiratory tissue mechanics in asymptomatic wheezy infants.

Low-frequency forced oscillation (LFOT) and raised volume rapid thoracic compression (RVRTC) techniques were used to measure airways and respiratory tissue mechanics and forced expiratory volumes in 24 asymptomatic infants with recurrent wheeze. Total respiratory impedance spectra (Zrs) (0.5 to 20 Hz) were obtained (n = 22) and a model containing airway (resistance [Raw] and inertance [Iaw]) and constant-phase tissue (tissue damping [G] and tissue elastance [H]) compartments fitted to Zrs. Forced expiratory volumes (FEV(0.5)) were determined (n = 16). Standardized variants (Z scores) were calculated for comparison to a healthy population (Hall et al., Am J Respir Crit Care Med 2000;162:1397-1402). Wheezy infants had elevated H (Z scores: 0.61 +/- 0.20; p = 0.007) but not Raw (0.14 +/- 0.25; p > 0.2), G (0.41 +/- 0.21; p = 0.066), or FEV(0.5) (-0.25 +/- 0.25; p > 0.2) compared with healthy infants. Infants younger than 1 yr of age were not significantly different from normals, whereas lung function from infants older than 1 yr had deviated from normal infants, with Z scores of 0.58 +/- 0.2 (p = 0.018), 0.79 +/- 0.31 (p = 0.032), 1.06 +/- 0.25 (p = 0.002), and -0.94 +/- 0.22 (p = 0.007) for Raw, G, H, and FEV(0.5) respectively. We conclude that asymptomatic infants with recurrent wheeze have altered lung function. The abnormalities were more pronounced in respiratory tissue mechanics than in airway mechanics or forced volumes, highlighting the value of techniques capable of partitioning lung function into airway and respiratory tissue components.

Child, Preschool↗

PubMed2001

Wearing a noseclip improves nebulised aerosol delivery.

OBJECTIVE: The efficiency of nebulised aerosol delivery is limited due to drug retained within the nebuliser, and due to a poor ratio between inspiratory drug delivery and expiratory drug loss. Several technical approaches have improved the ratio between inspiratory aerosol delivery and expiratory aerosol loss. In our pilot study we aimed to investigate if wearing a noseclip during inhalation therapy improves the inspiratory versus expiratory ratio and hence, improves nebulised aerosol delivery. METHODS: Drug delivery was measured in thirteen subjects (7 males; age range 23-36 years) inhaling in random order nebulised aerosol through a mouthpiece once while wearing a noseclip and once without. RESULTS: Wearing a noseclip leads to an increase of 113% (SEM 23.5) in drug delivery and improves the inspiratory versus expiratory ratio (ratio 2.07 versus 0.75). CONCLUSIONS: We have shown that aerosol delivery is increased due to an improved inspiratory versus expiratory ratio when wearing a noseclip.

Administration, Inhalation↗

PubMed2001

Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques.

BACKGROUND: The contribution of the pulmonary tissues to the mechanical behaviour of the respiratory system is well recognised. This study was undertaken to detect airway and lung tissue responses to inhaled methacholine (Mch) using the low frequency forced oscillation technique (LFOT). METHODS: The respiratory system impedance (Zrs, 0.5-20 Hz) was determined in 17 asymptomatic infants. A model containing airway resistance (Raw) and inertance (Iaw) and a constant phase tissue damping (G) and elastance (H) was fitted to Zrs data. Tissue hysteresivity (eta) was calculated as eta=G/H. The raised volume rapid thoracic compression technique (RVRTC) was used to generate forced expiratory volume in 0.5 seconds (FEV(0.5)). Lung function was determined at baseline and following inhaled Mch in doubling doses (0.25-16 mg/ml) until the maximal dose was reached or a fall of 15% in FEV(0.5) was achieved (PC(15)FEV(0.5)). The response to Mch was defined in terms of the concentration of Mch provoking a change in lung function parameters of more than two standard deviation units (threshold concentration). RESULTS: At PC(15)FEV(0.5) a response in Raw, Iaw, G, and eta, but not H, was detected (mean (SE) 61.28 (12.22)%, 95.43 (34.31)%, 46.28 (22.36)%, 44.26 (25.83)%, and -6.48 (4.94)%, respectively). No significant differences were found between threshold concentrations of LFOT parameters and FEV(0.5). CONCLUSIONS: Inhaled Mch alters both airway and respiratory tissue mechanics in infants.

Bronchoconstrictor Agents↗

PubMed2001

Effects of gestation and antenatal steroid on airway and tissue mechanics in newborn lambs.

The aim of this study was to partition airway and parenchymal mechanics in newborn lambs at different gestations and following variable exposure to antenatal maternal betamethasone using the forced oscillation technique (FOT). Pulmonary impedance data were collected in 37 sedated and intubated apneic lambs with the FOT between 0.5 and 20 Hz and fitted by a model to estimate airway resistance (Raw) and inertance (Iaw) and the coefficients of tissue resistance (GL) and elastance (HL). Total respiratory resistance (Rrs) was also determined during tidal ventilation by using the multiple linear regression technique. Advancing gestation or increasing antenatal steroid exposure had no clinically significant effect on the values of Raw and Iaw, whereas Rrs and both GL and HL decreased markedly. There was a decrease in tissue hysteresivity (GL/HL) with repeated antenatal steroid exposure. Partitioning of lung mechanics highlights the dominant contribution of the tissues to the total respiratory resistance in the immature ovine lung. Clinically relevant changes in lung mechanics associated with structural and functional maturation of the immature ovine lung are primarily confined to the tissue compartment.

Administration, Topical↗

PubMed2001

Evaluation of the interrupter technique in healthy, unsedated infants.

The interrupter technique may be used to monitor respiratory resistance and does not require active patient cooperation, but has yet to be applied in unsedated, spontaneously breathing infants. The aim of this study was to determine if the interrupter technique is feasible in spontaneously breathing infants and to investigate the influence of facemask types and analysis techniques on the interrupter resistance (Rint). Rint was measured in 14 healthy, unsedated, sleeping infants (aged 38.4 (31-56) days (mean (range)). Paired measurements were made using large volume, compliant (Mcomp) and small volume, rigid (Mrigid) facemasks. Flow and pressure were measured at the airway opening prior to- and following a brief airway occlusion (500 ms). Rint was calculated using four previously reported analysis techniques. Rint could be measured in all infants. Mcomp, independent of the analysis method significantly underestimated Rint (p<0.001). The variability and magnitude of Rint were significantly influenced by the choice of analysis method. The conclusion is that the interrupter technique is feasible in spontaneously breathing, unsedated infants. Equipment design and analysis method significantly influences interrupter resistance. Studies standardizing equipment and identifying the most appropriate analysis technique in this age group are needed.

Airway Resistance↗

PubMed2000

Reducing electrostatic charge on spacer devices and bronchodilator response.

AIMS: Plastic spacers are widely used with pressurized metered dose inhalers (pMDI). Reducing electrostatic charge by washing spacers with detergent has been shown to greatly improve in vitro and in vivo drug delivery. We assessed whether this finding is associated with an improved bronchodilator response in adult asthmatics. METHODS: Twenty subjects (age 18-65 years) with a known bronchodilator response inhaled in random order salbutamol from a pMDI (Ventolin) through an untreated new spacer (Volumatic) and through a detergent washed spacer. Patients received the following doses of salbutamol via pMDI at 20 min intervals: 100 microg, 100 microg, 200 microg, 400 microg, 800 microg. Spirometry, heart rate and blood pressure were checked prior to each dose and 20 min after the last dose. RESULTS: There were no differences between baseline forced expiratory volume in 1 s (FEV1) using either spacer (2.61+/-0.56 and 2.52+/-0.45 l, untreated and treated with detergent, respectively; mean +/- s.d.). The provocation dose required to cause a clinically significant improvement of 10% in FEV1 (PD10) was significantly lower when the detergent treated spacer was used (1505 +/-1335 and 430+/-732 microg, untreated and treated, respectively, P<0.002). CONCLUSIONS: We have demonstrated an improvement in bronchodilator response, in adult asthmatics, after reducing the electrostatic charge in a spacer device by washing it with ordinary household detergent. This finding stresses the importance of an optimal choice of delivery device for asthma medication.

Adolescent↗

PubMed2000

Airway and respiratory tissue mechanics in normal infants.

Low-frequency respiratory impedance (Zrs) was measured by applying a forcing signal, between 0.5 and 21 Hz at a transrespiratory pressure of 20 cm H(2)O, in a cross-sectional study of 37 normal infants. A model containing an airway resistance (Raw) and inertance (Iaw) and a tissue damping (G) and elastance (H) was fitted to the individual Zrs. Forced expiratory volume in 0.5 second (FEV(0.5)) was determined using the raised volume rapid thoracic compression technique. Multivariate regression analysis was used to analyze the relationships between the lung function parameters and length. Both airway and tissue parameters showed a decreasing quadratic relationship with increasing length. FEV(0.5) showed an increasing cubic relationship with length. A family history of asthma was found to have a negative effect on Raw, H, and FEV(0.5).

Airway Resistance↗

PubMed1999

Recall antigen presentation by gamma-interferon-activated microglia results in T cell activation and propagation of the immune response.

The interaction between microglia and T cells is important in the development of central nervous system inflammation. This may result in full T cell activation, a partial state of activation, anergy or apoptosis of the 'responding' T cell. Here, we demonstrate that neonatal rodent microglia not only fail to initiate a mixed lymphocyte reaction (MLR), but suppress background T cell proliferation. Even after activation with gamma-IFN or following phagocytosis, microglia remain unable to support a MLR. By contrast, gamma-IFN-activated microglia are able to activate memory T cells in a recall assay resulting in cytokine (gamma-IFN) release and modest T cell proliferation. Although the stimulation index is small, functional relevance is demonstrated. Supernatants from the recall assay stimulate gamma-IFN-dependent activation of a STAT (signal transducer and activator of transcription) factor within resting microglia. This demonstrates that memory T cells not only receive sufficient stimulation from the gamma-IFN-activated microglia to proliferate and produce cytokines, but that there is also a reciprocal stimulation of resting microglia. Importantly, this provides evidence that activated microglia have the potential to propagate immune responses in the central nervous system, but are unlikely to initiate a primary response.

Animals↗

PubMed1999

Repeat measurement of respiratory mechanics using the forced oscillation technique in non-paralysed rats.

The present study has established a method for obtaining low-frequency forced oscillation measurements of lung mechanics in the absence of neuromuscular blockade in the rat. Increasing the ventilation rate of the animals inhibited the spontaneous breathing of the animals for a short period of time; enough to make the low-frequency forced oscillation measurements of lung mechanics without the need for paralysis of the animals. Using this technique, it was possible to show that neuromuscular blockade with pancuronium bromide (0.4 mg/kg iv) resulted in a significant inhibition of methacholine responses in the parenchymal, but not the airway components of the rat lung. In studies where the animals were examined in a repeated manner, there was no significant difference in methacholine responses on day 3 compared with those obtained on day 1. Similarly, in animals that were both challenged with methacholine and lavaged, there was no significant difference in the methacholine responses or in the total and differential cell numbers obtained from the bronchoalveolar lavage fluid. Thus, this study presents a technique for obtaining low-frequency forced oscillation estimates of lung mechanics in non-paralysed rats and allows for repeated measures to be made in the same animals. In addition, this study has demonstrated that neuromuscular blockade has differential effects on methacholine responses in different parts of the lung.

Animals↗

PubMed1999

The route of antigen delivery determines the airway and lung tissue mechanical responses in allergic rats.

BACKGROUND: Previous results have shown tissue constriction in allergic animals following inhalation of an antigen. Further studies have demonstrated a differing response pattern in airway and parenchymal mechanics following inhaled (i.h.) or intravenous (i.v.) delivery of methacholine (MCh). OBJECTIVE: The purpose of this study was to compare the acute allergic response in airway and parenchymal mechanics following i.h. and i.v. antigen challenge. METHODS: Brown Norway rats were sensitized to ovalbumin (OVA). Rats were anaesthetized, paralysed, and thoracotomized, and lung input impedance (ZL) between 0.5 and 21 Hz was measured using small-amplitude pseudo-random oscillations at control, after saline, and for up to 1 h after either i.h. (n = 7) or i.v. (n = 5) administration of OVA. ZL was evaluated in terms of airway resistance (Raw) and inertance (Iaw), and a constant phase tissue parenchymal damping (G) and elastance (H). RESULTS: Following i.h. OVA challenge elevations were found in Raw [192 +/- 32 (SE) %], G (223 +/- 21%), and H (141 +/- 5%). Raw showed higher elevation after i.v. challenge (418 +/- 57%), whereas the elevation in G (278 +/- 30%) and H (130 +/- 4%) was approximately equal to those seen following inhalation of an antigen. CONCLUSIONS: Delivery (i.v.) of an antigen produces a significantly higher response in airway resistance, whereas inhaled antigen results in a mixed airway and parenchymal response.

Administration, Inhalation↗

PubMed1999

Measurements of exhaled nitric oxide with the single-breath technique and positive expiratory pressure in infants.

The aim of this study was to adapt the single-breath technique with positive expiratory pressure to measure exhaled nitric oxide (eNO) in infants. We hypothesized that exhaled eNO was greater in wheezy than in healthy infants. We studied 30 infants (16 wheezy and 14 healthy). The forced expiratory volume in 0.5 s (FEV0.5) was determined with the raised volume rapid thoracic compression technique, and eNO was measured during constant expiratory flow with a rapid-response chemiluminescence analyzer. After passive inflation to a preset pressure of 20 cm H2O, thoracic compression with an inflatable jacket caused forced expiration to occur through a face-mask with an expiratory flow resistor attached. During the forced expiration, the jacket pressure was increased to maintain a constant driving mouth pressure and hence a constant expiratory flow (50 ml/s). The mean level of eNO in the wheezy infants (31.8 ppb) was significantly higher than the level in healthy infants (18.8 ppb) (p = 0.03). A family history of atopy in parents was associated with increased eNO levels (p < 0.001) independent of age, sex, weight, length, wheezing, and FEV0.5. We conclude that the single-breath technique with positive expiratory pressure is a feasible method for measuring eNO in infants. Levels of eNO were significantly higher in wheezy infants and in those with a family history of atopy.

Feasibility Studies↗

PubMed1998

Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations.

For studies investigating the mechanisms underlying the development of allergic conditions such as asthma, noninvasive methodologies for separating airway and parenchymal mechanics in animal models are required. To develop such a method, seven Brown Norway rats were studied on three occasions over a 14-day period. After the baseline measurements, on the third day inhaled methacholine was administered. Once lung function returned to the baseline level, a thoracotomy was performed to compare the lung mechanics in the intact- and open-chest conditions. On each occasion, the rats were anesthetized, paralyzed, and intubated. Small-amplitude oscillations between 0.5 and 21 Hz were applied through a wave tube to obtain respiratory impedance (Zrs). Esophageal pressure was measured to separate Zrs into pulmonary (ZL) and chest wall (Zw) components. A model containing a frequency-independent resistance and inertance and a tissue component, including tissue damping and elastance, was fitted to Zrs, ZL, and Zw spectra. Measurements of Zrs, ZL, or Zw and the model parameters calculated from them did not differ among tests. The number of animals required to show group changes in lung mechanics was significantly lower when animals were measured noninvasively than when the group changes were calculated from open-chest measurements. In conclusion, the method reported in this study can be used to separate airway and lung tissue mechanics noninvasively over a series of tests and can detect pulmonary constrictor responses for the airways and the parenchyma separately.

Aerosols↗